Bleeding complications of antiangiogenic therapy: pathogenetic mechanisms and clinical impact.

Tumor vasculature and tumor-associated neo-angiogenesis have recently become major targets of antineoplastic therapy. Beside the agents which have already obtained US Food and Drug Administration (FDA) approval for clinical use (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib), many others are being tested in clinical trials. Angiogenesis inhibitors, in particular inhibitors of the vascular endothelial growth factor (VEGF) pathway, have shown significant vascular complications, including both thromboembolic and bleeding events. The definition of the clinical impact of bleeding complications (increase in the rate of hemorrhages in comparison with the control group) and the knowledge of the pathogenesis of this toxicity are very important in order to evaluate the results of many studies using antiangiogenic agents in the treatment of cancer patients.